Ventricular electrical storm after Micra™ leadless pacemaker implant.

Peri- and post-procedural ventricular tachycardia (VT) is a rare complication after leadless pacemaker implantation and requires an individualized approach. In this case report we describe the management of VT in a patient with subendocardial scarring due to prior coronary artery disease who presented with monomorphic VT the day after implant. The etiology was found to be related to the novel ventricular activation wavefront by ventricular pacing which induced a reentrant circuit dependent on pre-existing myocardial substrate. Invasive electrophysiologic study and ablation is a safe and successful treatment strategy in selected patients with evidence of myocardial scarring.

Itraconazole for COVID-19: preclinical studies and a proof-of-concept randomized clinical trial.

BACKGROUND: The antifungal drug itraconazole exerts in vitro activity against SARS-CoV-2 in Vero and human Caco-2 cells. Preclinical and clinical studies are required to investigate if itraconazole is effective for the treatment and/or prevention of COVID-19. METHODS: Due to the initial absence of preclinical models, the effect of itraconazole was explored in a clinical, proof-of-concept, open-label, single-center study, in which hospitalized COVID-19 patients were randomly assigned to standard of care with or without itraconazole. Primary outcome was the cumulative score of the clinical status until day 15 based on the 7-point ordinal scale of the World Health Organization. In parallel, itraconazole was evaluated in a newly established hamster model of acute SARS-CoV-2 infection and transmission, as soon as the model was validated. FINDINGS: In the hamster acute infection model, itraconazole did not reduce viral load in lungs, stools or ileum, despite adequate plasma and lung drug concentrations. In the transmission model, itraconazole failed to prevent viral transmission. The clinical trial was prematurely discontinued after evaluation of the preclinical studies and because an interim analysis showed no signal for a more favorable outcome with itraconazole: mean cumulative score of the clinical status 49 vs 47, ratio of geometric means 1.01 (95% CI 0.85 to 1.19) for itraconazole vs standard of care. INTERPRETATION: Despite in vitro activity, itraconazole was not effective in a preclinical COVID-19 hamster model. This prompted the premature termination of the proof-of-concept clinical study. FUNDING: KU Leuven, Research Foundation - Flanders (FWO), Horizon 2020, Bill and Melinda Gates Foundation.

Which QT Correction Formulae to Use for QT Monitoring?

BACKGROUND: Drug safety precautions recommend monitoring of the corrected QT interval. To determine which QT correction formula to use in an automated QT-monitoring algorithm in our electronic medical record, we studied rate correction performance of different QT correction formulae and their impact on risk assessment for mortality. METHODS AND RESULTS: All electrocardiograms (ECGs) in patients >18 years with sinus rhythm, normal QRS duration and rate <90 beats per minute (bpm) in the University Hospitals of Leuven (Leuven, Belgium) during a 2-month period were included. QT correction was performed with Bazett, Fridericia, Framingham, Hodges, and Rautaharju formulae. In total, 6609 patients were included (age, 59.8±16.2 years; 53.6% male and heart rate 68.8±10.6 bpm). Optimal rate correction was observed using Fridericia and Framingham; Bazett performed worst. A healthy subset showed 99% upper limits of normal for Bazett above current clinical standards: men 472 ms (95% CI, 464-478 ms) and women 482 ms (95% CI 474-490 ms). Multivariate Cox regression, including age, heart rate, and prolonged QTc, identified Framingham (hazard ratio [HR], 7.31; 95% CI, 4.10-13.05) and Fridericia (HR, 5.95; 95% CI, 3.34-10.60) as significantly better predictors of 30-day all-cause mortality than Bazett (HR, 4.49; 95% CI, 2.31-8.74). In a point-prevalence study with haloperidol, the number of patients classified to be at risk for possibly harmful QT prolongation could be reduced by 50% using optimal QT rate correction. CONCLUSIONS: Fridericia and Framingham correction formulae showed the best rate correction and significantly improved prediction of 30-day and 1-year mortality. With current clinical standards, Bazett overestimated the number of patients with potential dangerous QTc prolongation, which could lead to unnecessary safety measurements as withholding the patient of first-choice medication.